Keynote address: the influence of microenvironmental factors on the activity of radiation and drugs.

The inherent radio- and chemosensitivity of tumor cells clearly affects their response to treatment. Accumulating evidence, however, suggests that the biochemical and physiological status of the cell during treatment is at least as important. In this review, a critique of the current evidence for, and extent of, microenvironmental heterogeneity in tumors is presented, emphasizing human tumor cells in situ. The expected consequences of those changes on cellular response to radiation and chemotherapy is then briefly reviewed. Finally, the continuing interest in developing new therapeutic strategies for which the tumor microenvironment is an asset (as opposed to a liability) is discussed in the context of the dynamic nature of tumors, and the complexity of adequately analyzing combination treatments.